The human T-cell lymphotropic virus type 1 (HTLV-I) was the first retrovirus shown to be causally related to a specific human malignancy, adult T-cell leukemia/lymphoma (ATLL) (Poiesz, et al. Proc. Natl. Acad. Sci. U.S.A.77.7415-7419., Yoshida, M., I. Miyoshi, and Y. Hinuma, et. al. Proc. Natl. Acad.Sci.USA 79:2031-2035). Recently it was found that the same virus was also associated with a chronic myelopathy in the tropics and in southwestern Japan, HTLV-I-associated tropical spastic paraparesis (HTLV-I/TSP) (Johnson, et. al. Ann.Neurol 21:113-116., Gessain, et. al. Lancet 2:407-410., Rodgers-Johnson et. al. Lancet 2:1947-1248., Vernant, et. al. Ann.Neurol 21:123-130.) or HTLV-I-associated myelopathy (HAM) (Osame, et. al. Lancet 1:1031-1032.) The development of these two different diseases in HTLV-I infected individuals may depend in part on differences in the nature of patient T-cell responses to HTLV-I because there is some indication of an HLA phenotype-association with the risk of ATLL and TSP/HAM among HTLV-I seropositive individuals, (Usuku et. al. Ann.Neurol 23:S143-S150. This HLA association of neurologic manifestations of HTLV-I infection can be correlated with a difference in lymphocyte proliferative response to the virus, namely, a high response in TSP/HAM and low response in ATLL. For these reasons, it was important to identify epitopes of HTLV-I recognized by T cells, in order to begin to test the hypothesis that T-cell responses to different HTLV-I epitopes might result in either protective immunity or autoimmune disease. Because of the difficulty of testing a large number of potential epitopes in patients, we have chosen to first identify potent T-cell epitopes in mice. Experience from influenza (Lamb, et. al. Nature 300:66-69., Hurwitz J. Immunol 133:3371-3377,) HIV, (Cease et. al. Proc. Natl. Acad. Sci. USA 84:4249-4253., Berzofsky et. al. Nature 334:706-708) and malaria (Good et. al. Science 235:1059-1062., Good et. al. Proc. Natl. Acad. Sci. USA 85:1199-1203., Dontfraid et. al Mol. Biol. Med., Sinigaglia et. al Nature 336:778-780) indicate a good correlation between epitopes recognized by murine T cells and those recognized by human T cells.
DeLisi and Berzofsky (Delisi et. al. Proc. Natl. Acad. Sci. U.S.A. 82:7048-7052) analysed the sequences of immunodominant sites of protein antigens and found that most of the T-cell epitopes corresponded to regions that could fold as amphipathic helices. An improved computer algorithm "AMPHI" was developed for the prediction of amphipathic helical structures in proteins (Margalit et. al. J. Immunol. 138:2213-2229) and applied to the prediction of immunodominant helper T-cell sites in the HIV-1 envelope protein (Cease et. al. Proc.Natl.Acad.Sci.USA 84:4249-4253) and Plasmodium falciparum malaria circumsporozoite protein (Good et. al. Science 235:1059-1062., Good et. al. Proc. Natl. Acad. Sci. USA 85:1199-1203).